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    Hollow microneedle assisted intradermal delivery of hypericin lipid nanocapsules with light enabled photodynamic therapy against skin cancer

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    Authors
    Abd-El-Azim, H.
    Tekko, I. A.
    Ali, A.
    Ramadan, A.
    Nafee, N.
    Khalafallah, N.
    Rahman, T.
    McDaid, William
    Aly, R. G.
    Vora, L. K.
    Bell, S. J.
    Furlong, F.
    McCarthy, H. O.
    Donnelly, R. F.
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    Affiliation
    School of Pharmacy, Queen's University Belfast,
    Issue Date
    2022
    
    Metadata
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    Abstract
    Photodynamic therapy (PDT) to manage non-melanoma skin cancers has garnered great attention over the past few years. Hypericin (Hy) is a potent lipid-soluble photosensitiser with promising anticancer therapeutic activities. Nevertheless, its poor water-solubility, aggregation in biological systems and insufficient skin penetration restricted its effective exploitation. Herein, we report for the first-time encapsulation of Hy into lipid nanocapsules (Hy-LNCs), and then application of an AdminPen™ hollow microneedles (Ho-MNs) array and an in-house fabricated Ho-MN to enable efficient intradermal delivery. The physicochemical properties, photoactivity, ex vivo drug distribution and cellular uptake were evaluated. Results showed that Hy-LNCs were successfully formed with a particle size of 47.76 ± 0.49 nm, PDI of 0.12 ± 0.02, high encapsulation efficiency (99.67% ± 0.35), 396 fold higher photoactivity, 7 fold higher skin drug deposition, significantly greater cellular uptake and higher photocytotoxicity compared to free Hy. The therapeutic effect of Hy-LNCs was finally assessed in vivo using a nude mouse model with transplanted tumours. Interestingly, Hy-LNCs delivered by Ho-MN exhibited remarkable anti-tumour destruction (85.84%) after irradiation with 595 nm. This study showed that Ho-MNs-driven delivery of Hy-LNCs followed by irradiation could form a promising minimally invasive, effective and site-specific approach for managing non-melanoma skin cancers.
    Citation
    Abd-El-Azim H, Tekko IA, Ali A, Ramadan A, Nafee N, Khalafallah N, et al. Hollow microneedle assisted intradermal delivery of hypericin lipid nanocapsules with light enabled photodynamic therapy against skin cancer. Vol. 348, Journal of Controlled Release. Elsevier BV; 2022. p. 849–69.
    Journal
    Journal of Controlled Release
    URI
    http://hdl.handle.net/10541/625384
    DOI
    10.1016/j.jconrel.2022.06.027
    PubMed ID
    35728715
    Additional Links
    https://dx.doi.org/10.1016/j.jconrel.2022.06.027
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.jconrel.2022.06.027
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